POS0872 SERUM LEVEL OF SOLUBLE INTERLEUKIN-2 RECEPTOR IS LINKED TO BETA2-MICROGLOBULINE, NT-PRO BNP AND HIGH-SENSITIVITY TROPONIN T AND MAY HELP TO IDENTIFY PATIENTS WITH EARLY CLINICAL PROGRESS IN SSc.
Authors: L. Schumacher, S. Klapa, A. Müller, G. Riemekasten
Journal: Annals of the Rheumatic Diseases (2022)

Background Systemic sclerosis (SSc) is characterized by chronic inflammation that leads to damage of the vascular endothelium and excessive collagen deposition in several target organs (1). The interaction of interleukin 2 (IL-2) with the corresponding receptor (IL-2R) is involved in the regulation of autoimmune processes (2). The shedding product of the IL-2R alpha chain, soluble IL-2 receptor (sIL-2R, CD25), is able to either reduce or enhance immune responses (2). Previously, elevated serum levels of sIL-2R were found in the bronchoalveolar lavage of SSc patients with interstitial lung disease (SSc-ILD) as well as serologically in patients with early SSc, and thus suggested to be a biomarker for clinical development of SSc (3,4). Objectives To examine concentrations of sIL-2 in patients with SSc and analyse their association with clinical and serological parameters. Methods To determine if serological levels of sIL-2R serve as predictor of clinical complications in SSc, sera were analysed [limited cutaneous SSc (lcSSc) n=160; diffuse cutaneous SSc (dSSc), n=137] using a sandwich ELISA. Clinical data (pulmonary fibrosis, PAH, mRSS, therapy) and serological markers (hs-CRP, NT-pro BNP, neutrophil counts, creatinine, hs-troponin T, creatinine kinase, beta2-microglobuline) were assessed at the time of serum sampling and up to 48 months after baseline. Clinical progress was defined by the need to change therapies. Results Patients with dSSc presented elevated levels of sIL-2R compared to SSc (dSSc: 673±428 U/ml vs. 646±473 U/ml, p=0.0001). In SSc general, sIL-2R levels correlated with beta2-microglobuline (r=0.6161, p&lt;0.0001, ROC-AUC:0.8428), hs-CRP (r=0.4091, p&lt;0.0001, ROC-AUC:0.7110), NT-proBNP (r=0.2610, p&lt;0.0001, ROC-AUC:0.6793), neutrophil count (r=0.2749, p&lt;0.0001) and hs-troponin T (r=0.4548, p&lt;0.0001, ROC-AUC:0.8729). Further, sIL-2R levels discriminated normal from pathological levels of hs-troponin T (sensitivity 80.0%, specificity 80.1%). Using Log-rank test and Mantel-Cox proportional hazard models, we found that sIL-2R levels above 745.5 U/ml predicted early clinical progress in SSc (HR: 3.45, p=0.0070, Figure 1) within 12 months. Figure 1. Kaplan-Meier survival analysis for the complete group of patients with SSc. Soluble Il-2R levels above 745U/ml were associated with early progress in SSc. Conclusion In SSc, serum levels of sIL-2R could be of diagnostic value by identifying clinical progress. Its role in pathophysiology, especially with regard to disease manifestations such as cardiac involvement needs to be investigated in more detail. References [1]Blagojevic J et al. Use of vasoactive/vasodilating drugs for systemic sclerosis (SSc)-related digital ulcers (DUs) in expert tertiary centres: results from the analysis of the observational real.life DeSScipher study. Clin Rheumatol. 2020Jan;39(1):27-36. [2]Damoiseaux J The Il-2-Il-2 receptor pathway in health and disease: The role of the soluble IL-2 receptor. Clin Immunol 2020;Sep;218:108515 [3]Martinez JA et al. Elevation of soluble interleukin-2 receptor levels in thebronchoalveolar lavage from patients with systemic sclerosis . Rheumatol Int. 2001 Nov;21(3):122-6 [4]Valentini G et al. Early systemic sclerosis: short-term disease evolution and factors predicting the development of new manifestations of organ involvement. Arthritis Res Ther 2012 Aug17;14(4):R188 Disclosure of Interests None declared